The Treatment of Persistent Knee Effusions with Intra-articular Radioactive Gold: Preliminary Report

Eighteen chronic knee effusions unresponsive to the usual methods of therapy were treated by intra-articular injections of radioactive gold (¹⁹⁸Au) and followed up for one year. Ten patients had classical rheumatoid arthritis; three intermittent hydrarthrosis (both knees were treated in one patient); two ankylosing spondylitis, and one synovitis of undetermined cause. In 12 knees the effusion completely disappeared, usually within three months. Temporary increased pain and swelling occurred during the first week in five cases. Radiation dosimetry is discussed in detail.     

Etanercept in the treatment of recalcitrant enteropathic arthritis: a case report

Introduction

Enteropathic arthritis is one of the recognized extraintestinal manifestations of inflammatory bowel disease and affects up to 25% of patients. The treatment options for refractory disease were rather limited and ineffective until the arrival of biologic therapy in the last few years. The use of etanercept was unique for this disease.

Case presentation

In this case report, a 58-year-old Malay woman with a 17-year history of ulcerative colitis had persistent left knee effusion and synovitis for seven years, despite remission of the primary disease. She had had multiple courses of systemic and intra-articular steroid that caused significant systemic side effects such as impaired fasting glucose, hypertension, cataract, and weight gain. She also had a total left knee replacement for secondary osteoarthritis. But the left knee synovitis and effusion recurred a month after the total knee replacement, and she was subjected to a total synovectomy the following year. In view of failure of remission despite multiple immunosuppressants (100 mg of azathioprine daily, 1 g of sulfasalazine twice a day, 10 mg of prednisolone daily, and 10 mg of methotrexate weekly), 25 mg of subcutaneous etanercept twice weekly was started. After 5 weeks of treatment, complete resolution of left knee effusion and normalization of the inflammatory markers were shown. This continued up to 12 months of follow-up while our patient was on etanercept and 10 mg of methotrexate weekly. No relapse or serious side effects were noted.

Conclusions

This case demonstrates the efficacy of etanercept in recalcitrant enteropathic arthritis with no relapse of the underlying colitis while on treatment. The usage of this tumor necrosis factor inhibitor was unique in this case of rheumatology and gastroenterology.     

The clinical spectrum and treatment of Lyme disease

Lyme disease was recognized as a separate entity because of close geographic clustering of affected children in Lyme, Connecticut, with what was thought to be juvenile rheumatoid arthritis. It then became apparent that Lyme disease is a complex, multisystem disorder. The illness usually begins in summer with erythema chronicum migrans and associated symptoms (stage 1). Weeks to months later, some patients develop neurologic or cardiac abnormalities (stage 2), and weeks to years later, many patients develop intermittent attacks of arthritis (stage 3), which may become chronic, with erosion of cartilage and bone. Patients with severe and prolonged illness have an increased frequency of the B-cell alloantigen, DR2. For patients with early Lyme disease, tetracycline appears to be the most effective drug, then penicillin, and finally erythromycin. High-dose intravenous penicillin is effective for the later stages of the disease.     

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis (RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines (e.g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-γ at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA.     

Decline in the frequencies of Borrelia burgdorferi OspA161 175-specific T cells after antibiotic therapy in HLA-DRB1*0401-positive patients with antibiotic-responsive or antibiotic-refractory lyme arthritis

Synovitis in patients with antibiotic-refractory Lyme arthritis persists for months to several years after antibiotic therapy. This course, which may result from infection-induced autoimmunity, is associated with T cell recognition of Borrelia burgdorferi outer surface protein A (OspA(161-175)) and with HLA-DR molecules that bind this epitope, including the DRB1*0401 molecule. In this study, we used tetramer reagents to determine the frequencies of OspA(161-175)-specific T cells in samples of PBMC and synovial fluid mononuclear cells (SFMC) from 13 DRB1*0401-positive patients with antibiotic-responsive or antibiotic-refractory arthritis. Initially, three of the six patients (50%) with antibiotic-responsive arthritis and four of the seven patients (57%) with antibiotic-refractory arthritis had frequencies of OspA(161-175)-specific CD4(+) T cells in peripheral blood above the cutoff value of 4 per 10(5) cells. Among the five patients with concomitant PBMC and SFMC, four (80%) had OspA tetramer-positive cells at both sites, but the mean frequency of such cells was 16 times higher in SFMC, reaching levels as high as 1,177 per 10(5) cells. In the two patients in each patient group in whom serial samples were available, the frequencies of OspA(161-175)-specific T cells declined to low or undetectable levels during or soon after antibiotic therapy, months before the resolution of synovitis in the two patients with antibiotic-refractory arthritis. Thus, the majority of patients with Lyme arthritis initially have increased frequencies of OspA(161-175)-specific T cells. However, the marked decline in the frequency of such cells with antibiotic therapy suggests that persistent synovitis in the refractory group is not perpetuated by these cells.     

Outcome predictors of intra-articular glucocorticoid treatment for knee synovitis in patients with rheumatoid arthritis – a prospective cohort study

Introduction

Intra-articular glucocorticoid treatment (IAGC) is widely used for symptom relief in arthritis. However, knowledge of factors predicting treatment outcome is limited. The aim of the present study was to identify response predictors of IAGC for knee synovitis in patients with rheumatoid arthritis (RA).

Methods

In this study 121 RA patients with synovitis of the knee were treated with intra-articular injections of 20 mg triamcinolone hexacetonide. They were followed for six months and the rate of clinical relapse was studied. Non-responders (relapse within 6 months) and responders were compared regarding patient characteristics and knee joint damage as determined by the Larsen-Dale index. In addition, matched samples of serum and synovial fluid were analysed for factors reflecting the inflammatory process (C-reactive protein, interleukin 6, tumour necrosis factor alpha, vascular endothelial growth factor), joint tissue turnover (cartilage oligomeric matrix protein, metalloproteinase 3), and autoimmunity (antinuclear antibodies, antibodies against citrullinated peptides, rheumatoid factor).

Results

During the observation period, 48 knees relapsed (40%). Non-responders had more radiographic joint damage than responders (P = 0.002) and the pre-treatment vascular endothelial growth factor (VEGF) level in synovial fluid was significantly higher in non-responders (P = 0.002).

Conclusions

Joint destruction is associated with poor outcome of IAGC for knee synovitis in RA. In addition, higher levels of VEGF in synovial fluid are found in non-responders, suggesting that locally produced VEGF is a biomarker for recurrence of synovial hyperplasia and the risk for arthritis relapse.     

新型非骨水泥柄设计特征及临床应用效果

目的:探讨一种新型的适合于儿童的非骨水泥固定型股骨柄设计特征,并通过随访获得其临床效果。方法:选取2010年9月~2013年4月在我科植入新型非骨水泥股骨柄的6名儿童患者,其中男1例,女5例;年龄8.5±3.2岁(5~11岁)。病理诊断结果骨肉瘤患者5例,恶性神经鞘瘤患者1例;右股骨下端患者5例,左股骨下端患者1例;其中一例患者术前有病理骨折。6例患者在我科行双动半膝关节置换术,其中股骨下端均采用了新型非骨水泥假体柄。采用Enneking骨肌肉肿瘤置换后下肢功能评定标准对患肢行功能评价,影像学重点评估股骨柄在髓腔放置位置是否得当、股骨柄假体有无松动、有无应力遮挡、骨溶解等现象,并测量术后患者患肢短缩畸形数据。结果:6例患者随访时间32个月(14~54个月),除1例5岁女童术前肢体条件较差在术后14个月行膝关节融合手术,其余无翻修病例,置换关节均无感染、折断等现象。MSTS评分21.33分;射线片示所有患者股骨髓腔内假体柄放置位置满意,股骨侧及胫腓骨侧假体周围未见骨溶解。结论:新型非骨水泥固定型股骨柄设计合理,早期稳定性可,后期可取得满意的生物固定效果。     

Gallbladder carcinoma: a retrospective analysis of twenty-two years experience of a single teaching hospital

BACKGROUND: The purpose of this study was to retrospectively evaluate our experience with gallbladder cancer since the establishment of a tumour registry in our institute. METHODS: Between 1975 and 1998, 23 consecutive patients with gallbladder cancer were identified using the tumour registry database. There were 18 females (78%) and 5 (22%) males. The mean age at diagnosis was 70.6 (range 42-85) years. The diagnosis was achieved either intra-operatively or following the histological analysis of the gallbladder (n = 17), following gallbladder or liver biopsy (n = 4) or at autopsy (n = 2). Presenting symptoms included upper abdominal pain, weight loss, nausea, vomiting, fever, painless jaundice, hepatomegaly, upper abdominal mass, upper abdominal tenderness, and gastrointestinal haemorrhage. RESULTS: Histological examination revealed 20 adenocarcinomas (87%), 2 squamous cell carcinomas (9%) and one spindle cell sarcoma (4%). At presentation, 14 (61%) gallbladder cancers were stage IV, 5 (22%) were stage III and 4 (17%) were stage II. Kaplan Meier analysis revealed a mean survival of 3.2, 7.8 and 8.2 months for stage IV, III, and II disease respectively. Out of 14 patients with stage IV disease, 8 patients received adjuvant chemotherapy and survived for 4.6 months whereas six patients who did not receive adjuvant chemotherapy survived for 1.3 months. This difference was statistically significant (p = 0.04). CONCLUSION: The majority of patients with gallbladder cancer presented with advanced stage disease (stage IV) which carries a dismal prognosis. Patients who received chemotherapy with stage IV disease, however, did better than those who did not, but this is probably a reflection of patient selection.     

Synovial fluid leukocyte apoptosis is inhibited in patients with very early rheumatoid arthritis

Synovial leukocyte apoptosis is inhibited in established rheumatoid arthritis (RA). In contrast, high levels of leukocyte apoptosis are seen in self-limiting crystal arthritis. The phase in the development of RA at which the inhibition of leukocyte apoptosis is first apparent, and the relationship between leukocyte apoptosis in early RA and other early arthritides, has not been defined. We measured synovial fluid leukocyte apoptosis in very early arthritis and related this to clinical outcome. Synovial fluid was obtained at presentation from 81 patients with synovitis of < or = 3 months duration. The percentages of apoptotic neutrophils and lymphocytes were assessed on cytospin preparations. Patients were assigned to diagnostic groups after 18 months follow-up. The relationship between leukocyte apoptosis and patient outcome was assessed. Patients with early RA had significantly lower levels of neutrophil apoptosis than patients who developed non-RA persistent arthritis and those with a resolving disease course. Similarly, lymphocyte apoptosis was absent in patients with early RA whereas it was seen in patients with other early arthritides. The inhibition of synovial fluid leukocyte apoptosis in the earliest clinically apparent phase of RA distinguishes this from other early arthritides. The mechanisms for this inhibition may relate to the high levels of anti-apoptotic cytokines found in the early rheumatoid joint (e.g. IL-2, IL-4, IL-15 GMCSF, GCSF). It is likely that this process contributes to an accumulation of leukocytes in the early rheumatoid lesion and is involved in the development of the microenvironment required for persistent RA.     

Purine metabolism and clinical status of patients with rheumatoid arthritis treated with dipyridamole

The anti-inflammatory activities of methotrexate and sulphasalazine may be mediated by increases in endogenous adenosine levels. Since the vascular protective drug dipyridamole inhibits the uptake and metabolism of adenosine we have now tested this compound in patients with rheumatoid arthritis to assess its effects on their symptoms. Forty patients (aged 18-75 years) received dipyridamole 400 mg/day or placebo. The levels of adenosine and its major metabolites were determined by high performance liquid chromatography (HPLC) in blood samples taken at baseline and at monthly intervals during treatment for 6 months. After three months of treatment there was a significant reduction in the modified Health Assessment Questionnaire (mHAQ) score, but these effects were not maintained, and dipyridamole did not modify disease severity scores or the levels of adenosine and its metabolites. We conclude that the symptoms of rheumatoid arthritis were not modified by treatment with dipyridamole.     

Purine Metabolism and Clinical Status of Patients with Rheumatoid Arthritis Treated with Dipyridamole

The anti-inflammatory activities of methotrexate and sulphasalazine may be mediated by increases in endogenous adenosine levels. Since the vascular protective drug dipyridamole inhibits the uptake and metabolism of adenosine we have now tested this compound in patients with rheumatoid arthritis to assess its effects on their symptoms. Forty patients (aged 18–75 years) received dipyridamole 400 mg/day or placebo. The levels of adenosine and its major metabolites were determined by high performance liquid chromatography (HPLC) in blood samples taken at baseline and at monthly intervals during treatment for 6 months. After three months of treatment there was a significant reduction in the modified Health Assessment Questionnaire (mHAQ) score, but these effects were not maintained, and dipyridamole did not modify disease severity scores or the levels of adenosine and its metabolites. We conclude that the symptoms of rheumatoid arthritis were not modified by treatment with dipyridamole.     

Early antibiotic treatment of reactive arthritis associated with enteric infections: clinical and serological study.

OBJECTIVE--To find out whether a 10-14 days'' course of antibiotics early in the course of reactive arthritis associated with enteric infections could reduce the severity and duration of the disease and whether the antibody response in patients with reactive arthritis associated with yersinia infection differed between those treated and those not treated with the antibiotics. DESIGN--Prospective multicentre trial in which patients were randomised to treatment or no treatment with antibiotics. Patients were seen at three and six weeks and three, six, nine, 12, and 18 months after their first visit. SETTING--Departments of infectious diseases in three hospitals in Linköping, Malmö, and Stockholm, Sweden. PATIENTS--40 Consecutive patients who had had symptoms of reactive arthritis associated with enteric infection for less than four weeks. INTERVENTIONS--20 Patients were allocated to treatment with antibiotics and 20 patients did not receive antibiotics. All patients received non-steroidal anti-inflammatory drugs, and four also received intra-articular steroid injections after at least six weeks'' observation. MAIN OUTCOME MEASURES--Arthritic symptoms assessed clinically and by using Ritchies'' index; blood measurements reflecting inflammatory activity; serum IgG, IgM, and IgA antibody titres; HLA tissue type. RESULTS--No difference was observed concerning duration of arthritis, grade of inflammation, and number of joints affected between patients treated and those not treated with antibiotics. Furthermore, there was no significant difference between the two groups in erythrocyte sedimentation rate and haptoglobin, IgG, and IgA concentrations. All values had returned to normal within three months. No patient developed chronic arthritis, but sustained slight arthralgia occurred in three patients. The HLA-B27 antigen was found in 23 (58%) of the patients, and its presence did not affect clinical outcome. The IgG, IgM, and IgA antibody responses were similar in patients treated with antibiotics and those not treated. CONCLUSION--Short term antibiotic treatment has no beneficial effect on the clinical outcome of reactive arthritis associated with enteric infection.     

Patients with rheumatoid arthritis in clinical remission and ultrasound-defined active synovitis exhibit higher disease activity and increased serum levels of angiogenic biomarkers

Introduction

The aim of this study was to identify and characterize subclinical synovitis in patients with rheumatoid arthritis (RA) in clinical remission using power Doppler ultrasound (PDUS) and serum levels of biomarkers of inflammation and/or angiogenesis.

Methods

We selected patients with RA in clinical remission defined as a Disease activity score of 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) <2.6 for more than six months tested by two independent rheumatologists. Clinical, epidemiological, demographic and serological data were analyzed. PDUS of knees and hands was performed by a sonographer. Synovial hypertrophy (SH) and PDUS signal were scored (grades 0 to 3). SH ≥2 and a PDUS signal was classified as active synovitis. Serum levels of biomarkers of inflammation/angiogenesis were determined by Quantibody^® Human Array.

Results

This study included 55 patients, of whom 25 (45.4%) met criteria for ultrasound-defined active synovitis. Patients with active synovitis had higher DAS28-C reactive protein (P = 0.023), DAS28-ESR (P = 0.06), simplified disease activity score, SDAI (P = 0.064), and only 12% were taking oral glucocorticoids (≤5 mg/day) compared with 40% of patients without active synovitis (P = 0.044). Patients with synovitis also had significantly higher serum levels of the angiogenic biomarkers angiopoietin-2 (P = 0.038), vascular endothelial growth factor-D (P = 0.018), placental growth factor (P = 0.043), stromal cell-derived factor-1 (P = 0.035), matrix metallopeptidase-2 (P = 0.027) and basic fibroblast growth factor (bFGF) (P = 0.007), but not of pro-inflammatory cytokines.In the multivariate logistic regression model used to explore prognostic biomarkers for active synovitis, serum levels of bFGF, DAS28-ESR and not receiving glucocorticoids were the best predictors of active synovitis. The predictive indexes provided by the model were specificity 73.3%, sensitivity 72%, and area under the curve in receiver operating characteristic 81.5% (95% CI: 70.1% to 92.8%).

Conclusions

Nearly half of the patients with RA in clinical remission had ultrasound-defined active synovitis, higher disease activity and less frequent oral glucocorticoid consumption than patients without active synovitis. This clinical situation was associated with a specific biological profile characterized by an excess of angiogenic mediators rather than persistent proinflammatory cytokine responses.     

Characterization of histopathology and gene-expression profiles of synovitis in early rheumatoid arthritis using targeted biopsy specimens

The disease category of early rheumatoid arthritis (RA) has been limited with respect to clinical criteria. Pathological manifestations of synovitis in patients whose disease is clinically classified as early RA seem to be heterogeneous, with regular variations. To clarify the relation between the molecular and histopathological features of the synovitis, we analyzed gene-expression profiles in the synovial lining tissues to correlate them with histopathological features. Synovial tissues were obtained from knee joints of 12 patients with early RA by targeted biopsy under arthroscopy. Surgical specimens of long-standing RA (from four patients) were examined as positive controls. Each histopathological parameter characteristic of rheumatoid synovitis in synovial tissues was scored under light microscopy. Total RNAs from synovial lining tissues were obtained from the specimens selected by laser capture microdissection and the mRNAs were amplified by bacteriophage T7 RNA polymerase. Their cDNAs were analyzed in a cDNA microarray with 23,040 cDNAs, and the levels of gene expression in multilayered lining tissues, compared with those of normal-like lining tissues in specimens from the same person, were determined to estimate gene-expression profiles characteristic of the synovial proliferative lesions in each case. Based on cluster analysis of all cases, gene-expression profiles in the lesions in early RA fell into two groups. The groups had different expression levels of genes critical for proliferative inflammation, including those encoding cytokines, adhesion molecules, and extracellular matrices. One group resembled synovitis in long-standing RA and had high scores for some histopathological features – involving accumulations of lymphocytes and plasma cells – but not for other features. Possible differences in the histopathogenesis and prognosis of synovitis between the two groups are discussed in relation to the candidate genes and histopathology.     

RUBELLA ARTHRITIS—A Study of Twenty Cases

Twenty patients, five males and fifteen females, who had rubella arthritis were observed for periods ranging from one to ten years after recovery.Rubella arthritis in these patients was characterized by polyarthritis associated with fibrositis, myalgia, paresthesias and muscular weakness. All of the male patients but only one-third of the females had involvement of the knee joints. The small joints of the hands were the joints most commonly affected in women. Post-rubella arthritis rheumatic symptoms, especially fibrositis, persisted for many months in almost half of the females, not at all in the males.The leukocyte content of the blood tended to be low and the erythrocyte sedimentation rate accelerated in the few patients in which determinations were done.Latex tests were performed in 17 patients. Ten of the 17 were studied with the three-stage technique of Hall. Results of inhibition tests were positive in 80 per cent of the patients with rubella arthritis studied who were tested within 18 months after the onset of illness. None of the patients tested 18 months or more after rubella arthritis had positive reaction.     

Comparative Effectiveness of Etanercept and Adalimumab in Patient Reported Outcomes and Injection-Related Tolerability

Objective

To describe patient preferences in selecting specific biologics and compare clinical response using patient reported outcomes (PROs) among patients with rheumatoid arthritis (RA) started on different anti-tumor necrosis factor (TNF) therapies.

Methods

Participants were enrollees in Kaiser Permanente Northern California. Patients with RA who had at least two provider visits and started a new anti-TNF therapy from 10/2010–8/2011, were eligible for participation in this longitudinal study. Using a telephone survey, patient preferences in biologic selection and RAPID3, MDHAQ, and SF-12 scores were collected at baseline and at 6 months. Patient scores rating injection/infusion-site burning and stinging (ISBS) were collected at 6 months.

Results

In all, 267 patients with RA responded to the baseline survey, of whom 57% preferred an injectable biologic, 22% preferred an infused biologic, and 21% had no preference. Motivation for injectable biologics was convenience (92%) and for infusion therapy was dislike or lack of self-efficacy for self-injection (16%). After 6 months of treatment with anti-TNF, 70% of the 177 patients who answered the ISBS question reported ISBS with the last dose; on a scale of 1 (none) to 10 (worst), 41% of these reported a score of 2–5; and 29% reported a score of 6–10. Adalimumab users experienced 3.2 times (95% confidence interval 1.2–8.6) the level of ISBS that etanercept users experienced. There were no significant differences in RAPID3, MDHAQ, or SF-12 scores between etanercept or adalimumab initiators.

Conclusion

Convenience and fear of self-injection were important considerations to patients selecting a biologic drug. Although more convenient, adalimumab associated with more ISBS than did etanercept, and this rate was higher than reported in clinical trials. At 6 months, PROs did not differ between etanercept and adalimumab users.     

Characteristics of Graves Disease in HIV-Infected Patients on Antiretroviral Therapy

ObjectiveTo demonstrate clinical and laboratory characteristics of Graves disease in human immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART).MethodsThis is a single-institution study. All HIV-infected Thai patients who were diagnosed with Graves disease following the initiation of ART between January, 2007, and June, 2018, were retrospectively enrolled.ResultsOf the 24 subjects, the mean age was 39.6 ± 10 years at the time of Graves disease diagnosis. The male to female ratio was 1:1.2. Palpitation and weight loss were the most common clinical manifestations. Of the 6 patients (25%) with evidence of Graves orbitopathy, 1 had sight-threatening orbitopathy. Two patients also had other autoimmune diseases (vitiligo and psoriatic arthritis). The median CD4 cell counts at HIV and Graves disease diagnosis were 73.5 (interquartile range &lsqb;IQR], 15.5 to 189.5) and 525 (IQR, 402.3 to 725) cells/μL, respectively. The median time from ART commencement of the last effective ART regimen to the development of Graves disease was 29.5 (IQR, 13.8 to 48) months with a mean CD4 cell count increment of 328.7 ± 174.9 cells/μL. The median duration of antithyroid therapy was 34.5 (IQR, 23.8 to 51.0) months. Thirteen patients (54.2%) received radioactive iodine ablation.ConclusionGraves disease should be suspected in HIV-infected patients who present with palpitations and weight loss despite good immunologic response to ART. Awareness of this condition can lead to diagnosis and appropriate management. Unlike immune reconstitution disease associated with infection, Graves disease may develop many years after ART initiation.     

Role of magnetic resonance imaging in the detection of chondral and osteochondral lesions in chronic juvenile arthritis

Chronic juvenile arthritis (CJA) is the most common inflammatory disease of joints in children. There are numerous studies showing the limited informative value of X-ray in the evaluation of CJA progression. Contrast-enhanced magnetic resonance imaging (MRI) using intravenous gadolinium is currently in the foreground in diagnosing arthritis in children, in infants in particular. Knee joints are most frequently afflicted in CJA, showing significant manifestations of the disease. The purpose of the study was to describe the patterns of changes in the nonossified epiphyseal and articular cartilages in the distal epiphyses of femurs in the knee joints of patients with manifestations of chronic juvenile arthritis and to define the role of contrast-enhanced MRI in evaluating the epiphyseal changes in this disease. Sixty-nine patients aged 1.5-14 years who have clinical laboratory and ultrasound signs of CJA lasting 6 months to 5 years underwent contrast-enhanced MRI for the evaluation of changes in the articular and nonossified epiphyseal cartilages. Intravenous contrast enhancement identified several specific features and patterns of epiphyseal changes: subchondral hyperemia of epiphyses and recorded thickened epiphyseal chondral vascular channels, chondral and osteochondral erosions as manifestations of changes in the growing epiphyseal cartilage and articular one in children with chronic arthritis. Thus, contrast-enhanced MRI allows differentiation of different patterns of epiphyseal changes in CJA.     

Efficacy of benzbromarone in hyperuricemic patients associated with chronic kidney disease

We have retrospectively evaluated the uric acid control status and renal function changes over a period of up to 7 years in 35 patients with renal impairment who had stage 3 or higher chronic kidney disease (CKD; stage 3 in 32 patients, stage 4 in 2 patients, and stage 5 in 1 patient) associated with hyperuricemia and were receiving monotherapy with benzbromarone as an antihyperuricemic drug. Serum uric acid levels significantly decreased from 8.5 ± 0.9 to 6.1 ± 0.8 mg/dL at 6 months and were subsequently controlled at less than 7.0 mg/dL in most patients. Most patients received benzbromarone at a dose of 25-50 mg/day, whereas 150-200 mg/day was used in some patients with stage 4 or 5 CKD. No significant changes in estimated glomerular filtration rate (eGFR) from the baseline value of 46.2 ± 11.5 mL/minute/1.73 m(2) were found after benzbromarone therapy. Although the renal function impairment did not improve by reducing the serum uric acid levels with benzbromarone, the renal function did not deteriorate further on the therapy. These results suggest that benzbromarone is applicable to the management of hyperuricemia associated with renal impairment.